ABSTRACT
The relationship between folic acid and S-adenosylhomocysteine (SAH) is controversial. This study aims to explore the effect of different doses of folic acid supplementation on SAH levels in hypertensive patients and the modification of methylene-tetrahydrofolate reductase (MTHFR) C677T gene polymorphism. A randomized, double-blind, controlled clinical trial was conducted. Hypertensive patients aged 45-75 years without a history of stroke and cardiovascular disease were selected, who were randomly assigned to one of 8 dose groups. This trial has been registered with Trial Number: ChiCTR1800016135. In the total population, folic acid supplementation of 0.4-2.0â mg/day had no effect on SAH level (ßâ =â 0.47, 95% CI: -0.86-1.79, pâ =â 0.491), while folic acid supplementation of 2.4â mg/day significantly increased SAH level (ßâ =â 1.93, 95% CI: 0.22-3.64, pâ =â 0.027). Stratified analysis found that MTHFR C677T genotype CC supplemented with 2.4â mg/day folic acid had no effect on SAH level (ßâ =â 0.30, 95% CI: -2.74-3.34, pâ =â 0.847), while CT and TT genotype supplemented with 2.4â mg/day folic acid showed a significant increase in SAH level (CT: ßâ =â 2.98, 95% CI: 0.34-5.62, pâ =â 0.027; TT: ßâ =â 3.00, 95% CI: -0.51-6.51, pâ =â 0.095; CT combined with TT: ßâ =â 2.99, 95% CI: 0.90-5.09, pâ =â 0.005). In conclusion, supplementation of 2.4â mg/day folic acid can lead to increased SAH levels, especially in MTHFR C677T genotype CT and TT.